Inflammation Flashcards
What is inflammation?
Response of living tissue to injury
Acute inflammation features
Immediate Short Limits damage Innate (built in) Stereotyped - same response each time
Phases of inflammation and aims
Vascular phase - changes blood flow, accumulates exudate
Cellular phase - delivers neutrophils
How is inflammation controlled
Chemical mediators
What’s an cause inflammation
Trauma/foreign body
Microorganisms
Hypersensitivity (allergies)
Other illness (cancer, necrosis)
5 clinical signs of inflammation
Rubor (red) Calor (hot) Dolor (pain) Tumor (swelling) Loss of function
Vascular changes in vascular phase and what they achieve
Vasoconstriction (seconds) Vasodilation (minutes) (redness and heat) Increased permeability (swelling)
Starlings law
Movement of fluid is controlled by:
Hydrostatic pressure and oncotic pressure
(High hydrostatic pressure pushes fluids out, high oncotic pressure pulls fluid in - sponge)
What do the vascular changes achieve?
Vasodilation - increased capillary hydrostatic pressure
Increased vessel permeability - plasma proteins move to interstitium (increases interstitial oncotic pressure)
FLUID MOVES OUT OF VESSEL INTO INTERSTITIUM = OEDEMA
What happens as a result of fluid moving out of capillaries/vessels?
Increased viscosity of blood
Reduced flow = stasis
Exudate (how and what is it)
Caused by increased vascular permeability
Protein rich
Occurs in inflammation
Transudate (how and what)
Permeability unchanged
Movement due to - increased capillary hydrostatic pressure/reduced capillary oncotic pressure
Occurs in: heart, hepatic, renal failure
How does a vessel wall become permeable? (3 ways)
Retraction of endothelial cells (histamine, nitric oxide, leukotrienes)
Direct injury (burns, toxins, trauma)
Leukocyte dependent injury (enzymes/toxic oxygen species released by active inflammatory cells)
Why is the vascular phase effective? (3 ways)
Interstitial fluid increase dilutes toxins
Exudate delivers proteins (fibrin limits spread via mesh prison, immunoglobulins delivered)
Fluid drains to lymph nodes (delivers antigens - stimulate adaptive response)
Main cell involved in cellular phase
Neutrophil - trilobed nucleus (appear purple dots on histology)
How do neutrophils escape vessels (4 stages)
Margination - move to periphery of vessel
Rolling - via selectins
Adhesion - via integrins
Emigration (diapedesis) - moves to interstitium
How do selectins work?
Present on activated endothelial cells
Activated by chemical mediators
Responsible for ROLLING
How do integrins work?
Present on neutrophil surface
Change from low affinity to high affinity
Responsible for ADHESION
How do neutrophils move through interstitium?
Chemotaxis - Movement along an increasing chemical gradient (low —> high) of chemoattractants
Chemoattractants: and what it achieves
Bacterial peptides, inflammatory mediators
Causes rearrangement of neutrophil cytoskeleton to propel itself forward
What do neutrophils do?
Phagocytosis
Into vesicle = phagosome
Fuse with lysosomes = phagolysosome
Release lysozymes and digest —> exocytosis
Also release inflators mediators
How do neutrophils recognise what to phagocytose?
Opsonins on pathogen - C3b, Fc
Receptors for C3b and Fc are on neutrophil surface
Killing mechanisms of neutrophils
Oxygen dependent - ROS ( superoxide, hydroxyl, hydrogen peroxide) or RNS (nitric oxide, nitrogen dioxide)
Oxygen independent - lysozyme, hydrolytic enzymes, defensins
Why is the cellular phase effective?
Removes pathogens and necrotic tissue
Releases inflammatory mediators
What are inflammatory mediators
Chemical messengers - control and coordinate inflammatory response
Where can inflammatory mediators arise from
Activated inflammatory cells
Platelets
Endothelial cells
Toxins (chemoattractants)
Inflammatory mediators that cause vasodilation
Histamine
Serotonin
Prostaglandins
Nitric oxide
Inflammatory mediators that increase permeability
Histamine
Bradykinin
Leukotrienes
C3a, C5a
Mediators that act as chemoattractants
C5a
TNF - a
IL - 1
Bacterial peptides
Inflammatory mediators that cause fever
Prostaglandins
IL-1
IL-6
TNF-a
Inflammatory mediators that cause pain
Bradykinin
Substance P
Prostaglandins
Complications of inflammation can be:
Local (tissue, organ) or systemic (whole body)
Local complications (SELP)
Swelling - compression of tubes (airways, bile duct, intestines)
Exudate - compress organs (cardiac tamponade in pericardial sac)
Loss of fluid - burns = dehydration
Pain - muscle atrophy., psychosocial effects
Systemic complications
Fever - pyrogens act on hypothalamus (eg prostaglandins)
Leucocytosis - increased white cell production (act on bone marrow IL-6, TNF-a)
Acute phase response
Septic shock
Acute phase response and proteins
Malaise, reduced appetite, altered sleep, tachycardia
Induces rest
Proteins:
C reactive protein (CRP= inflammation severity marker)
Fibrinogen
A1 antitrypsin
Septic shock
Huge release of chemical mediators Wide spread VASODILATION Hypotension Tachycardia Multi organ failure FATAL
After acute inflammation
Resolution
Repair with connective tissue
Chronic inflammation
Complete resolution
Mediators have short half lives
Vessel and permeability return to normal
Neutrophils = apoptosis and phagocytosed
Exudate drains into lymphatics
Regeneration of tissue if architecture is preserved
Repair with connective tissue
Fibrosis if substantial tissue destruction
Chronic inflammation
Prolonged inflammation with repair
Itis =
Inflammation
appendicitis cause
Blocked lumen from faecolith (solid poo)
Accumulation of bacteria and exudate
Increased pressure can cause burst appendix
Appendicitis symptoms
Vague abdominal pain
Sharp tight lower right fossa pain
Severe overall pain
Cause and symptoms pneumonia
Streptococcus pneumoniae
Haemophilus influenzae
Shortness of breath
Cough
Yellow/green sputum
Fever
Risk factors pneumonia
Smoking
Pre existing lung condition (COPD, asthma, malignancy)
Bacteria meningitis causes and symptoms
Cause:
Group B streptococcus
E.coli
Neisseria meningitides
Symptoms/signs: Headache Neck stiffness Photophobia (bright lights) Altered mental state
What happens during meningitis?
Inflammation of meninges (protective layers between skull and brain)
DURA, ARACHNOID, PIA (mater) - layers
Compression of brain occurs
Abscess
Accumulation of dead and dying neutrophils (pus)
Liquefactive necrosis
Compression of surrounding structures
Inflammation of serous cavities
Pleural, peritoneal, pericardium
Disorders of acute inflammation
Hereditary angio-oedema
Alpha-1 antitrypsin deficiency
Chronic granulomatous disease
